Recent studies have resulted in a characterization of the antigenic determinant of antigen B of Timothy grass pollen. The antigen is composed of a flavanoid pigment, quercitin; a disaccharide, cellobiose; and a polypeptide "tail". Antigen B is the generic name for mixtures containing two or more antigen fragments conventionally termed "antigen D, D.sub.1, D.sub.2, D.sub.3, etc. They differ from each other in the length of the polypeptide "tail". In antigen D.sub.3, the "tail" consists of a single aminoacid, namely, threonine. See Malley et al, Dev. Biol. Stand., 1975, 29 (Int. WHO-IABS, Symp. Stand. Control Allergens Adm. Man., 1974), 29-40; Kramer-Kleinert et al, Dev. Biol. Stand., 1975, 29 (Int. WHO-IABS, Symp. Stand. Control Aller- gens Adm. Man., 1974), 188-96; Malley et al, Immunochemistry, 1975, Vol. 12, pages 551-554; Malley et al, Journal of Allergy, Vol. 43, No. 2, February, 1969, pages 59-64; Gerard et al, Immunochemistry, 1975, Vol. 12, pages 545-9; Malley et al, Journal of Immunology, Vol. 99, No. 4 (1967), pages 825-830; Sanderson et al, Immunology, Vol. 20 (1971), pages 1061-1065; and Axen et al, Nature, Vol. 214 (1967), pages 1302-1304.
In co-pending application Ser. No. 731,414, filed Oct. 12, 1976, now U.S. Pat. No. 4,140,679 it is disclosed that the various antigen D fragments coupled to various proteins or peptides through the free carboxyl group of threonine initiate significant histamine release from sensitized tissue. It is further disclosed therein, however, that these same antigen D fragments coupled to various proteins and peptides through the sugar moiety give rise to a dose-dependent inhibition of histamine release from sensitized tissue.
These studies intimate strongly that quercitin represents the major portion of the antigenic determinant of antigen B.
Antigen B and its various fragments may be represented by the structural formula: ##STR1## wherein G represents glucose and T represents threonine or a peptide linked to said structure through the threonine molecule.
Antigen D.sub.1 has the structure set forth above wherein the peptide tail is such that the molecular weight is about 5,000. Antigen D.sub.2 has a molecular weight of about 2,500. In antigen D.sub.3, T is threonine alone.
The quercitin fraction of the antigen structure is linked to the glucose moieties via an ether linkage through OH groups on the respective molecules. The threonine linkage to the glucose moiety is also an ether linkage through an OH group on the cellobiose fraction and the OH group of threonine.
The nature of the allergic reaction or response in humans and animals is not completely understood. It is theorized that the allergic response to a foreign antigen, such as the antigen of grass pollen, involves the interaction of at least two different cell types. One of these is conventionally termed a T-cell, or Thymus derived lymphocyte, and the second a B-cell, which is a bone marrow derived lymphocyte. Each of these two cells, the T and the B lymphocytes, recognize different parts of the protein that causes the allergic response. The B-lymphocyte recognizes the antigenic determinant whereas the T-lymphocyte recognizes a different portion of the protein, termed a carrier determinant. To achieve suppression of the immune response involved in allergic diseases one can attack the problem by either suppressing the formation of antibody by blocking B-cell differentiation or by affecting the T-cell population. The B-lymphocyte actually produces the antibody. T-cells do not produce the circulating antibody that is involved in allergic disease, but regulate their production. One sub-population of T-cells which assists in making antibodies are the so-called helper T-cells. They effectively cooperate or interact with the B-lymphocyte to produce antibodies. Another sub-population of T-cells, the "suppressor" T-cell or T.sub.s cell, effectively suppresses the action of helper T-cells so that they cannot participate with B-lymphocytes to produce antibodies.
It is an object of the present invention to provide a method for modifying the antigenic properties of Timothy antigen B and/or its various fragments to yield a product devoid of antigenic properties but capable of activating T-cells.